Bottom Line:
To date, no therapy has been found to satisfactorily treat SLE.Resveratrol also suppressed CD69 and CD71 expression on CD4+ T cells as well as CD4+ T cell proliferation, induced CD4+ T cell apoptosis, and decreased CD4 IFNγ+ Th1 cells and the ratio of Th1/Th2 cells in vitro.In vitro antibody production and proliferation of B cells were also inhibited.

Background: Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterized by the production of autoantibodies. To date, no therapy has been found to satisfactorily treat SLE. SIRT1 deficiency results in the development of an autoimmune syndrome in mice, including a high titer of anti-nuclear antibody in serum, immunoglobulin deposition in the kidney, and immune complex glomerulonephritis. Resveratrol is an activator of SIRT1 and possesses anti-inflammation and immune-regulatory properties.

Objective: To evaluate the preventative effects of resveratrol on a pristane-induced lupus animal model and assess its putative immune modulation effects.

Methods: BALB/c mice received a single intraperitoneal injection of 0.5 ml of pristane on day 1 and then various doses of resveratrol were given to the mice daily starting on day 2 and continuing for seven months. The autoantibodies in serum and supernatants were measured. Single cells isolated from spleen, isolated CD4+ T cells, and CD19+ B cells were cultured with or without resveratrol in vitro and assessed by flow cytometry.

Results: Resveratrol attenuated proteinuria, immunoglobuin depositon in kidney, and glomerulonephritis as well as IgG1 and IgG2a in serum in pristane-induced lupus mice. Resveratrol also suppressed CD69 and CD71 expression on CD4+ T cells as well as CD4+ T cell proliferation, induced CD4+ T cell apoptosis, and decreased CD4 IFNγ+ Th1 cells and the ratio of Th1/Th2 cells in vitro. In vitro antibody production and proliferation of B cells were also inhibited.

Conclusion: Resveratrol possesses protective effects in pristane-induced lupus mice and may represent a novel approach for the management of SLE.

pone-0114792-g003: Comparison of serum immunoglobulins at the end of the observation period.(A): IgG1 levels in mice of the resveratrol A group were significantly lower than those in the control group (n = 10 in each group). (B): Reduction of IgG2a levels in mice of the resveratrol A group (n = 10 in each group).

Mentions:
To assess the immune mechanisms responsible for the resveratrol-mediated prevention of ongoing pristane-induced lupus, we assessed its role in the regulation of humoral immunity by measuring total immunoglobulin levels and ANA as well as anti-ds-DNA and anti-RNP/Sm antibody levels in serum. At the end of the observation period, the IgG1 levels in mice from the resveratrol A group were significantly lower than those in the model control group (2.08±0.04 vs. 1.93±0.04, respectively; P<0.01; Fig. 3A). Similar findings were observed for IgG2a levels between the two groups (Fig. 3B), but no differences were observed in IgG2b, IgG3, IgM, and IgA levels between the treatment and the model control groups (data not shown). Similar results were also detected in mice from the resveratrol B group (data not shown).

pone-0114792-g003: Comparison of serum immunoglobulins at the end of the observation period.(A): IgG1 levels in mice of the resveratrol A group were significantly lower than those in the control group (n = 10 in each group). (B): Reduction of IgG2a levels in mice of the resveratrol A group (n = 10 in each group).

Mentions:
To assess the immune mechanisms responsible for the resveratrol-mediated prevention of ongoing pristane-induced lupus, we assessed its role in the regulation of humoral immunity by measuring total immunoglobulin levels and ANA as well as anti-ds-DNA and anti-RNP/Sm antibody levels in serum. At the end of the observation period, the IgG1 levels in mice from the resveratrol A group were significantly lower than those in the model control group (2.08±0.04 vs. 1.93±0.04, respectively; P<0.01; Fig. 3A). Similar findings were observed for IgG2a levels between the two groups (Fig. 3B), but no differences were observed in IgG2b, IgG3, IgM, and IgA levels between the treatment and the model control groups (data not shown). Similar results were also detected in mice from the resveratrol B group (data not shown).

Bottom Line:
To date, no therapy has been found to satisfactorily treat SLE.Resveratrol also suppressed CD69 and CD71 expression on CD4+ T cells as well as CD4+ T cell proliferation, induced CD4+ T cell apoptosis, and decreased CD4 IFNγ+ Th1 cells and the ratio of Th1/Th2 cells in vitro.In vitro antibody production and proliferation of B cells were also inhibited.

Background: Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterized by the production of autoantibodies. To date, no therapy has been found to satisfactorily treat SLE. SIRT1 deficiency results in the development of an autoimmune syndrome in mice, including a high titer of anti-nuclear antibody in serum, immunoglobulin deposition in the kidney, and immune complex glomerulonephritis. Resveratrol is an activator of SIRT1 and possesses anti-inflammation and immune-regulatory properties.

Objective: To evaluate the preventative effects of resveratrol on a pristane-induced lupus animal model and assess its putative immune modulation effects.

Methods: BALB/c mice received a single intraperitoneal injection of 0.5 ml of pristane on day 1 and then various doses of resveratrol were given to the mice daily starting on day 2 and continuing for seven months. The autoantibodies in serum and supernatants were measured. Single cells isolated from spleen, isolated CD4+ T cells, and CD19+ B cells were cultured with or without resveratrol in vitro and assessed by flow cytometry.

Results: Resveratrol attenuated proteinuria, immunoglobuin depositon in kidney, and glomerulonephritis as well as IgG1 and IgG2a in serum in pristane-induced lupus mice. Resveratrol also suppressed CD69 and CD71 expression on CD4+ T cells as well as CD4+ T cell proliferation, induced CD4+ T cell apoptosis, and decreased CD4 IFNγ+ Th1 cells and the ratio of Th1/Th2 cells in vitro. In vitro antibody production and proliferation of B cells were also inhibited.

Conclusion: Resveratrol possesses protective effects in pristane-induced lupus mice and may represent a novel approach for the management of SLE.